A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.Kidney International (2023) 103, 962-972; https://doi.org/10.1016/ j.kint.2023.02.022

Automated summary

A retrospective study was conducted on 203 cases of children with monogenic steroid-resistant nephrotic syndrome (SRNS) treated with a calcineurin inhibitor (CNI). The study found that a partial or full response was observed in a significant percentage of patients. Patients with higher serum albumin levels at the initiation of CNI treatment were more likely to achieve significant remission. These findings support the use of CNI treatment in children with monogenic SRNS.